Background. Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. Methods. BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-κB (NF-κB) pathway was determined by immunoblotting. Serum levels of inflammatory mediators—TNF-α, IL-1β, IL-6, IL-17A, and IL-23—were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes—catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)—was determined. Results. Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-κB pathway and JAK2/STAT3 signaling were significantly () downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis. Conclusion. The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-κB/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.

中文翻译：

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Punicalagin 通过调节 NF-κB-TH17/JAK2/STAT3 信号传导和氧化应激对强直性脊柱炎发挥保护作用

背景。强直性脊柱炎（AS）是一种慢性炎症性疾病，以骶髂关节炎和轴向关节的脊柱僵硬为特征。氧化应激和增加的促炎细胞因子的作用在 AS 发病机制中得到充分证明。Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose) 是一种广泛存在于石榴中的鞣花单宁，被发现具有有效的抗炎、抗增殖和抗氧化作用。本研究旨在调查 punicalagin 在 AS 啮齿动物模型中的作用。方法。在最后一次注射蛋白多糖提取物后 24 小时处死 BALB/c 小鼠诱发的脊柱炎。进行组织学评分以评估疾病的程度。JAK2/STAT3 蛋白和核因子蛋白的表达通过免疫印迹确定κB（NF-κB ）途径。评估了炎症介质——TNF- α、IL- 1β、IL-6、IL-17A 和 IL-23——的血清水平。脂质过氧化和活性氧（ROS）的水平被量化。确定了作为抗氧化酶（过氧化氢酶 (CAT)、谷胱甘肽过氧化物酶 (GPx) 和超氧化物歧化酶 (SOD)）活性量度的抗氧化状态。结果。Punicalagin 有效地改善了抗氧化状态并降低了脂质过氧化、ROS 产生和炎症介质的血清水平。NF-κB通路和 JAK2/STAT3 信号通路显着 ()下调。Punicalagin 有效地调节 Th17 细胞和 IL-17A/IL-23 轴产生的细胞因子。结论。观察结果表明，punicalagin 通过减少氧化应激和调节 NF- κ B/TH17/JAK2/STAT3 信号在 AS 中发挥保护作用因此，可以进一步探索 Punicalagin 作为治疗 AS 的有效候选化合物。